Hyaluronic acid or hyaluronan (HA) is a naturally occurring high molecular weight polysaccharide that consists of alternating N-acetyl-D-glucosamine and D-glucuronic acid monosaccharide units linked with alternating [beta] 1-3 glucoronidic and [beta] 1-4 glucosaminidic bonds. It is a commonly occurring glycosaminoglycan (GAG) in the body. The molecular weight of linear hyaluronic acid is generally within the range of 50,000 to 8,000,000 or more. Hyaluronic acid is present in cartilage, joint fluids, and skin tissue. It is plays a role in several biological processes in the body, such as moisturization and lubrication of tissues, and is used to treat joint disorders, promote wound healing and the formation of vessels.
Hyaluronic acid has also been widely employed in the treatment of skin. Commercially available cosmetic compositions often contain linear hyaluronic acid as a moisturizing agent. However, the utility of linear hyaluronic acid is sometimes limited by the fact that it is rapidly degraded by hyaluronidase in the body.
Cross-linked hyaluronic acid provides improved mechanical properties and in vivo residence time. For example, HyaCare® Filler CL, commercially available from Evonik Industries AG, is a wrinkle smoother comprising a water-in-oil emulsion containing small particles of cross-linked hyaluronic acid in a vehicle of water, ethylhexyl stearate, polyglyceryl-4 diisostearate/polyhydroxystearate/sebacate, and sodium isostearate. Hylasome® EG10, sold by Vantage Specialty Ingredients, is another example of commercially available cross-linked hyaluronic acid for skin care use.
Hyaluronic acid is also used commercially as injectable filler to address wrinkles and other signs of skin aging. However, injections are typically painful, particularly in the face, and must be administered by a medical professional. It would be desirable to deliver hyaluronic acid, particularly cross-linked hyaluronic acid, and other large, cosmetically acceptable active ingredients by topical administration, which is convenient and painless. However, the stratum corneum of mammalian skin presents a formidable barrier to the penetration. The ability of a substance applied to the skin surface to penetrate through the skin is inversely related to the thickness of the stratum corneum layer. In addition, permeation of cross-linked hyaluronic acid and other large molecules into the skin is made more difficult because of their size. The large polymeric structure that gives hyaluronic acid its beneficial effects also makes it difficult to administer topically.
Compositions and methods for the topical delivery of hyaluronic acid, including cross-linked hyaluronic acid, and other large molecules have now been identified. Specifically, the present inventors have found that low pH topical compositions containing a buffering agent having a pKa of about 2.8 to about 4.2 and providing a buffering capacity of at least 0.15 provide increased penetration of hyaluronic acid and other large cosmetically acceptable active ingredients having pKa's of about 2.8 to about 4 into mammalian skin. Methods of increasing the topical delivery of such cosmetically acceptable active ingredients are also provided.